Stereochemical Definition of the Natural Product (6<i>R</i>,10<i>R</i>,13<i>R</i>, 14<i>R</i>,16<i>R</i>,17<i>R</i>,19<i>S</i>,20<i>S</i>,21<i>R</i>,24<i>S</i>,25<i>S</i>,28<i>S</i>,30<i>S</i>,32<i>R</i>,33<i>R</i>,34<i>R</i>,36<i>S</i>,37<i>S</i>,39<i>R</i>)‐Azaspiracid‐3 by Total Synthesis and Comparative Analyses

Abstract

The previously accepted structure of the marine toxin azaspiracid-3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)-azaspiracid-3 chromatographically and spectroscopically matched naturally occurring azaspiracid-3, whereas the previously assigned 20R epimer did not.